Person:

Emilsson, Louise

Abstract Background: Celiac disease (CD) has been linked to cancer, especially lymphoproliferative malignancy (LPM). Earlier research has shown that first-degree relatives (FDRs) to individuals with CD are at increased risk of autoimmunity including CD, but data on their risk of cancer are scarce and contradictory. We aimed to assess whether Swedish FDRs to individuals with CD are at increased risk of cancer. Methods: Individuals with CD (identified through biopsy reports equal to Marsh grade III) were matched on sex, age, county, and calendar year with up to 5 control individuals. All FDRs (father, mother, sibling, offspring) of CD individuals (“celiac FDRs”: n = 109,391) and controls (n = 548,465) were identified through Swedish healthcare registries. Through Cox regression, we calculated hazard ratios (HRs) for cancer incidence (all cancer, breast cancer, gastrointestinal cancer, and LPM). Results: During follow-up, celiac FDRs experienced 10,750 unique cancers as opposed to 54,686 in-control FDRs. Celiac FDRs were at a slightly lower risk of any cancer (HR 0.97, 95% confidence interval [CI] 0.95–0.99), partially due to the lower risk of breast cancer (HR 0.92, 95% CI 0.87–0.98). The relative risks of LPM (HR 0.99, 95% CI 0.91–1.08) and gastrointestinal cancer (HR 0.98, 95%CI 0.93–1.03) were both close to 1. As opposed to earlier research, we found no excess risk of LPM in siblings to individuals with CD (HR 0.98, 95% CI 0.81–1.19). Conclusion: Celiac FDRs are not at increased risk of cancer, including LPM, arguing that shared genetics is unlikely to explain previous reports of an excess risk of LPM in patients with CD.

Objective: Earlier research suggests that birth weight may be associated with celiac disease (CD), but the direction of association has been unclear potentially due to confounding effect from genetic and intrafamilial factors. Through within-twin analyses, we aimed to minimize confounding effects such as twins that share genetic and early environmental exposures. Materials and methods Using the Swedish Twin Registry, we examined the birth weight of 146,830 twins according to the CD status. CD was defined as having villous atrophy according to a small intestinal biopsy reports. Results: The prevalence of diagnosed CD was 0.5% (n=669), and we included 407 discordant pairs of CD–non-CD twins. Comparing the 669 CD patients with non-CD twins, the association between birth weight and future CD was not statistically significant (odds ratio [OR] per 1000 g increase in birth weight: 1.16; 95% confidence interval [CI]=0.97–1.38). In males, the association was positive and statistically significant (OR=1.50; 95% CI=1.11–2.02). However, the association was not significant in within-pair analyses for both dizygotic and monozygotic twins and for both sexes. Conclusion: This population-based study found that in male twins, higher birth weight was associated with higher risk of CD. However, when comparing discordant twin pairs in within-twin pair analyses, there was no statistically significant association between birth weight, intrauterine growth, and future risk of CD.